Safety and efficacy of leflunomide in primary Sjögren's syndrome: A phase II pilot study

Background: For invalidating symptoms in primary Sjögren's syndrome (pSS), there is still a need for easy-to-administer, cost-effective and well-tolerated systemic treatment. Leflunomide (LEF) is structurally unrelated to other immunomodulatory drugs and might be efficacious in pSS, given its characteristic immunoregulatory modes of action. Objective: To investigate the safety and efficacy of LEF in pSS in a phase II open-label pilot study. Methods: 15 patients with pSS with early and active disease received LEF 20 mg once daily for 24 weeks. Tolerabilily, safety and efficacy of LEF were evaluated every 8 weeks. Additional safety visits were performed every fortnight. Results: Mild gastrointestinal discomfort (including diarrhoea) and hair loss were mainly reported. Five patients developed lupus-like skin lesions on the face, arms or trunk, responding well to topical corticosteroids, nevertheless causing the withdrawal of one patient. Two patients with pre-existing hypertension had to increase dosages of anti-hypertensive drugs. Increased levels of alanine aminotransferase normalised after dose reduction in two patients. A decrease in general fatigue and an increase in physical functioning were observed after 24 weeks. Serum IgG levels decreased from 8 weeks onwards. Schirmer test values increased, not reaching statistical significance, whereas sialometry values did not change. In four of five repeated biopsies, the lymphocytic focus score decreased at the rate of 1 focus/4 mm2. A remarkable amelioration of leucocytoclastic vasculitis was observed in three patients. Conclusions: Although the safety profile seems fairly acceptable, the observed indications for efficacy were modest and may be doubtful in justifying a randomised controlled trial of LEF in pSS.